The 5-pyrimidinemethanol, flurprimidol (1, α-isopropyl-α-[p-(trifluoromethoxy)phenyl]-5-pyrimidinemethanol, CAS #56425-91-3) is a plant-growth regulator currently marketed under the brand names Cutless® and Topflor® as well as a mixture with various other agrochemicals. In the United States, it is manufactured by SePRO Corporation (Carmel, Ind.). Flurprimidol was first described in U.S. Pat. No. 3,967,949. Its structure is depicted below:

Flurprimidol (1) is currently manufactured by the methodology illustrated in Scheme 1.

Briefly, p-(trifluoromethoxy)bromobenzene (2) is converted to p-(trifluoromethoxy) phenylmagnesium bromide and reacted with isobutyronitrile to afford isopropyl p-(trifluoromethoxy)phenyl ketone (3). The reaction of 3 with 5-bromopyrimidine 4 in the presence of n-BuLi affords 1. This reaction proceeds through the intermediacy of the lithiated intermediate 5. The conversion of 5-bromopyrimidine (4) to the 5-lithiopyrimidine (5) occurs without significant degradation only at or below −80° C. The cryogenic operation required to maintain such reaction conditions is expensive. The limited stability of 5 mandates the presence of 3 during the addition of n-butyllithium, which introduces impurities such as 6 and 7 in the final product.
